title: Efficacy and tolerability of besifloxacin ophthalmic suspension 0.6% administered twice daily for 3 days in the treatment of bacterial conjunctivitis: a multicenter, randomized, double-masked, vehicle-controlled, parallel-group study in adults and children.
abstract: BACKGROUND
  Besifloxacin is a topical fluoroquinolone with potent in vitro activity against a broad spectrum of ocular pathogens, including drug-resistant strains. Besifloxacin ophthalmic suspension 0.6% given 3 times daily for 5 days has been reported to be more effective than its vehicle in the treatment of bacterial conjunctivitis. Pharmacokinetic/pharmacodynamic modeling suggests that besifloxacin might also be effective given twice daily.
  
  
  OBJECTIVE
  This study evaluated the efficacy and tolerability of besifloxacin ophthalmic suspension 0.6% administered twice daily for 3 days compared with vehicle (formulation without besifloxacin) in the treatment of adults and children with bacterial conjunctivitis.
  
  
  METHODS
  This was a multicenter, prospective, randomized, double-masked, vehicle-controlled, parallel-group study. Patients aged ≥1 year with bacterial conjunctivitis were randomized to receive besifloxacin ophthalmic suspension or vehicle administered twice daily for 3 days. There were 3 study visits: the baseline visit, visit 2 (day 4 or 5), and visit 3 (day 7±1). Participants recorded the times of medication instillation in a patient diary. The primary end points were clinical resolution and bacterial eradication of the baseline bacterial infection at visit 2 in patients with culture-confirmed bacterial conjunctivitis. Secondary end points were clinical resolution and bacterial eradication of the baseline bacterial infection at visit 3, individual clinical outcomes (ocular conjunctival discharge and bulbar conjunctival injection) at the follow-up visits, and microbial and clinical outcomes for overall bacterial species and individual gram-positive and gram-negative bacterial species. Tolerability assessments included ocular adverse events (AEs), changes in visual acuity, biomicroscopy and ophthalmoscopy findings, and nonocular AEs.
  
  
  RESULTS
  Of 202 patients randomized to treatment (mean [SD] age, 25.2 [24.3] years; 56.9% female; 76.7% white), 109 had culture-confirmed bacterial conjunctivitis (53 besifloxacin ophthalmic suspension, 56 vehicle). At visit 2, the besifloxacin ophthalmic suspension group had significantly greater rates of clinical resolution compared with the vehicle group (37/53 [69.8%] vs 21/56 [37.5%], respectively; P < 0.001), as well as significantly greater rates of bacterial eradication (46/53 [86.8%] vs 32/56 [57.1%]; P < 0.001). At visit 3, rates of bacterial eradication were also significantly greater in the besifloxacin ophthalmic suspension group compared with the vehicle group (46/53 [86.8%] vs 39/56 [69.6%]; P = 0.038). Results for the individual clinical outcomes and microbial and clinical outcomes by gram-positive and gram-negative species were consistent with the primary efficacy outcomes. The incidence of ocular AEs did not differ significantly between treatment groups (4/94 [4.3%] vs 8/98 [8.2%]). Ocular AEs in all treated eyes in the respective groups included bacterial conjunctivitis (3/157 [1.9%] and 5/154 [3.2%]), conjunctivitis (3/157 [1.9%] and 4/154 [2.6%]), and allergic conjunctivitis (2/157 [1.3%] and 1/154 [0.6%]). These events were of mild or moderate severity. Changes in visual acuity and biomicroscopy and ophthalmoscopy findings were comparable between groups. There were few nonocular AEs (2/94 [2.1%] vs 3/98 [3.1%]; P = NS), none of them considered treatment related.
  
  
  CONCLUSIONS
  In these adults and children with bacterial conjunctivitis, treatment with besifloxacin ophthalmic suspension 0.6% administered twice daily for 3 days was effective and well tolerated. ClinicalTrials.gov identifier: NCT00972777.
authors.affiliation: Shasta Eye Medical Group, Inc., Redding, California, USA.
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Silverstein
authors.forename: Catherine
authors.initials: C
authors.lastname: Allaire
authors.forename: Kirk M
authors.initials: KM
authors.lastname: Bateman
authors.forename: Lynne S
authors.initials: LS
authors.lastname: Gearinger
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Morris
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Comstock
mesh_terms: D000287:Administration, Topical; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001381:Azepines / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D003234:Conjunctivitis, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D004311:Double-Blind Method; D005260:Female; D024841:Fluoroquinolones / Q000008:administration & dosage* / Q000009:adverse effects; D005500:Follow-Up Studies; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy / Q000382:microbiology; D006801:Humans; D007223:Infant; D008297:Male; D008853:Microscopy / Q000379:methods; D008875:Middle Aged; D009887:Ophthalmoscopy; D011446:Prospective Studies; D016896:Treatment Outcome; D014792:Visual Acuity / Q000187:drug effects; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D001381:Azepines; D024841:Fluoroquinolones; C522124:besifloxacin